Outsmarting the host: unraveling virus-host interactions and their impact on Usutu virus replication

Arthropod-borne viruses (arboviruses) are transmitted by arthropod vectors such as mosquitos or ticks. The risk of arbovirus outbreaks is increasing due to changes in climate and land use, increased international travel, and urbanization. To better prepare for future arbovirus outbreaks it is important to understand which factors influence the outcome of a viral infection. The interplay between the virus and the host largely determines this outcome. The research described in this thesis focused on better understanding the interactions between Usutu virus (USUV), an emerging arbovirus, and the host cell. Evasion of innate immune responses by viruses has been suggested to play an important role in the outcome of infection. Therefore, we first explored the interaction of USUV with the interferon response, an important branch of the mammalian innate immune response. Next, a broader and more unbiased approach was used to further unravel the interactions of the viral protein NS4A with the human host cell. We then showed that USUV can induce the autophagic response via NS4A. In addition, the development and characterization of different tools to support the study of virus-host interactions is described. One of the described tools includes the use of a 3D skin model to study arboviruses.